1. Field
The present disclosure relates to medicinal formulations that can, for example, contain sufficient amounts of parenteral omega-3 fatty acids derived from naturally-occurring marine oils, and that can function as a novel “therapeutic” drug carrier, or vehicle. This proposed novel application is in contrast to conventional “pharmaceutical” drug carriers, or vehicles.
The marine oil-containing formulations can be in the form of an emulsion drug vehicle, comprising omega-3 fatty acids, attached to triglyceride or ester molecules, as an oil component of the emulsion, in addition to a water component. These two components of the emulsion, with the aid of a suitable surfactant, can exist as separate, but miscible phases, along with one or more drugs that, when parenterally administered without accompanying omega-3 fatty acids-containing marine oil, would often be expected to cause collateral damage to a vital organ. The novel marine oil-containing formulation can be given by intravenous administration, as an oil-in-water emulsion containing the drug(s). The addition of the omega-3 fatty acids (for example, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and/or docosapentaenoic acid (DPA)) to formulations containing selected drugs can reduce at least one adverse event profile of those drugs upon intravenous administration. The at least one adverse event profile can result from a drug toxicity, and can be manifested by oxidative stress, inflammation, immune stimulation or ischemia of one or more vital organs, or a combination thereof.
2. Related Art
Bioactive omega-3, or n3, fatty acids (n3-FAs) are present in naturally-occurring marine oil triglycerides and are contained in a variety of commercial products as nutritional supplements, in such forms, for example, as soft gelatin capsules, foods, enteral nutrition formulations, and parenteral oil-in-water nutrition emulsions. As well, semi-synthetically-derived n3-FAs also exist in a highly purified form, such as omega-3 acid ethyl esters in liquid-filled capsules, used for the treatment of hypertriglyceridemia. The bioactive components of marine oils can consist of three main omega-3 fatty acids: namely, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and, to a lesser extent, docosapentaenoic acid (DPA).
In the critical care setting, the administration of clinical nutrition supplemented with omega-3 fatty acids in fish oil-containing lipid injectable emulsions has been shown to reduce mortality, the use of antibiotics and the length of hospital stay (Reference [8] and [17]). These general beneficial effects were observed in acutely ill surgical patients, but the specific reasons for these positive findings were not clear, as noted by the following excerpt from one of the study conclusions: “In view of the lack of substantial study literature concerning diagnosis-related nutritional single-substrate intervention in the critically ill, the present data can be used in formulating hypotheses . . . .” (Reference [8]). In other words, there is evidence to support the general, or nonspecific, clinical benefits of providing n3-FAs to acutely ill patients, but the reasons for these benefits are poorly understood.
By comparison, in critically ill medical patients, supplementation with fish oil parenteral nutrition emulsions did not affect inflammation or outcome (Reference [33]). Finally, in a recent review about the role of fish oil-containing parenteral nutrition emulsions, the following statement summarizes their present status in clinical medicine: “ . . . the influence on inflammatory processes, immune function and clinical endpoints is not clear, since there are too few studies and those that are available report contradictory findings” (Reference [31]). Due to the heterogeneity of patient populations, and the complex array of diseases and treatments, present application of n3-FAs as such, is non-specific. Moreover, there are significant qualitative differences with respect to available fish oil emulsions and various oil compositions (U.S. application Ser. No. 12/382,196 and International Application No. PCT/US2010/000723), further masking any potential clinical benefits.